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Genomic characterization of thymic epithelial tumors in a real-world dataset
BACKGROUND: Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594028/ https://www.ncbi.nlm.nih.gov/pubmed/37703595 http://dx.doi.org/10.1016/j.esmoop.2023.101627 |
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author | Kurokawa, K. Shukuya, T. Greenstein, R.A. Kaplan, B.G. Wakelee, H. Ross, J.S. Miura, K. Furuta, K. Kato, S. Suh, J. Sivakumar, S. Sokol, E.S. Carbone, D.P. Takahashi, K. |
author_facet | Kurokawa, K. Shukuya, T. Greenstein, R.A. Kaplan, B.G. Wakelee, H. Ross, J.S. Miura, K. Furuta, K. Kato, S. Suh, J. Sivakumar, S. Sokol, E.S. Carbone, D.P. Takahashi, K. |
author_sort | Kurokawa, K. |
collection | PubMed |
description | BACKGROUND: Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting. METHODS: We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated. RESULTS: A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma. CONCLUSIONS: To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development. |
format | Online Article Text |
id | pubmed-10594028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105940282023-10-25 Genomic characterization of thymic epithelial tumors in a real-world dataset Kurokawa, K. Shukuya, T. Greenstein, R.A. Kaplan, B.G. Wakelee, H. Ross, J.S. Miura, K. Furuta, K. Kato, S. Suh, J. Sivakumar, S. Sokol, E.S. Carbone, D.P. Takahashi, K. ESMO Open Original Research BACKGROUND: Thymic epithelial tumors (TETs) are rare neoplasms arising in the mediastinum, including thymic carcinomas and thymomas. Due to their rarity, little is known about the genomic profiles of TETs. Herein, we investigated the genomic characteristics of TETs evaluated in a large comprehensive genomic profiling database in a real-world setting. METHODS: We included data from two different cohorts: Foundation Medicine Inc. (FMI) in the United States and the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. Samples profiled were examined for all classes of alterations in 253 genes targeted across all assays. Tumor mutational burden (TMB) and microsatellite instability (MSI) were also evaluated. RESULTS: A total of 794 patients were collected in our study, including 722 cases from FMI and 72 cases from C-CAT. In the FMI data, CDKN2A (39.9%), TP53 (30.2%) and CDKN2B (24.6%) were frequently altered in thymic carcinoma, versus TP53 (7.8%), DNMT3A (6.8%), and CDKN2A (5.8%) in thymoma. TMB-high (≥10 mutations/Mb) and MSI were present in 7.0% and 2.3% of thymic carcinomas, and 1.6% and 0.3% of thymomas, respectively. Within C-CAT data, CDKN2A (38.5%), TP53 (36.5%) and CDKN2B (30.8%) were also frequently altered in thymic carcinoma, while alterations of TSC1, SETD2 and LTK (20.0% each) were found in thymoma. CONCLUSIONS: To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development. Elsevier 2023-09-12 /pmc/articles/PMC10594028/ /pubmed/37703595 http://dx.doi.org/10.1016/j.esmoop.2023.101627 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Kurokawa, K. Shukuya, T. Greenstein, R.A. Kaplan, B.G. Wakelee, H. Ross, J.S. Miura, K. Furuta, K. Kato, S. Suh, J. Sivakumar, S. Sokol, E.S. Carbone, D.P. Takahashi, K. Genomic characterization of thymic epithelial tumors in a real-world dataset |
title | Genomic characterization of thymic epithelial tumors in a real-world dataset |
title_full | Genomic characterization of thymic epithelial tumors in a real-world dataset |
title_fullStr | Genomic characterization of thymic epithelial tumors in a real-world dataset |
title_full_unstemmed | Genomic characterization of thymic epithelial tumors in a real-world dataset |
title_short | Genomic characterization of thymic epithelial tumors in a real-world dataset |
title_sort | genomic characterization of thymic epithelial tumors in a real-world dataset |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10594028/ https://www.ncbi.nlm.nih.gov/pubmed/37703595 http://dx.doi.org/10.1016/j.esmoop.2023.101627 |
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